The importance of saliva in the protective maintenance of the oral cavity has been the subject of extensive research during the past two decades. In particular, the ability of salivary secretions to modulate the pathogenesis of the oral bacteria has received considerable attention. However, the role of saliva in viral pathogenesis has not been well characterized. The goal of this proposal is to assess the non-immune properties of saliva in modulating the in vitro infectivity of three oral herpesviruses: Herpes Simplex (HSV 1), Cytomegalovirus (CMV), and Epstein- Barr Virus (EBV). Human submandibular/sublingual saliva (HSMSL) and human parotid saliva (HPS) will be assayed for: 1) viral neutralization, 2) cell protective, and/or 3) antiviral activities. Salivary molecules which modulate viral infectivity will be identified by Western transfer using defined immunological reagents. The "relevant" salivary constituents will be subjected to various enyzmatic and/or chemical treatments to selectively modify structural domains. The modified product will then be compared with the intact molecule for reactivity in the in vitro assays listed above. Subsequently, minimal structural domains (e.g. purified and chemically characterized (glyco)peptides of "relevant" salivary molecules) will be compared and used directly or as inhibitors in the in vitro viral assay systems. Those salivary constituents which are involved in the viral neutralization and cell protective activity will be photoaffinity labeled with an iodinatable heterobifunctional, probe to identify the salivary receptors on viral particles and/or host cell surface. Finally, the concentrations of relevant salivary constituents will be determined in the salivas of normals and immunologically compromised individuals (e.g. individuals with Acquired Immunological Deficiency Syndrome or AIDS). The data obtained could contribute to the understanding of the in vivo pathogenesis of recurrent herpesvirus infections and provide new insight into the non-immune protective mechanisms of saliva in individuals with severe immunodeficiencies.